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SLE is a chronic multisystem autoimmune disease that affects the kidneys in approximately 50% of patients, with the prevalence rising to as high as 70% in certain populations, such as African American and Asian people. Antimalarials—and particularly hydroxychloroquine (HCQ)—are currently considered a mainstay of therapy, together with immunosuppressants. Over the past decades, several studies have extensively investigated the mechanisms of action of antimalarial agents and their potential beneficial properties in patients with SLE in general. However, the evidence for the therapeutic benefit of HCQ in patients with lupus nephritis (LN) derives mainly from observational studies, conducted in an era before the refinement of induction and maintenance protocols for immunosuppressive therapy. Despite the paucity of high-quality evidence on its efficacy in LN, the nephrology community widely supports the universal use of HCQ in patients with LN, and recommendations for its use are firmly entrenched in various clinical practice guidelines. Nonetheless, the use of antimalarials may also carry inherent risks, underscoring the importance of personalized approaches in these patients. Herein, we comprehensively review the available literature on antimalarials in LN, aiming to update the current evidence, limitations, and future perspectives for the use of antimalarials in adults.

Background: Value is defined as the ratio of patient outcomes to the cost of care. One method to assess value is through patient-level value analysis (PLVA). To our knowledge, this tool has not previously been implemented in the setting of total hip arthroplasty (THA). The purposes of this study were to perform PLVA for a 1-year episode of care among patients undergoing primary THA and to identify characteristics that affect value in a metropolitan health-care system. Methods: The patient-reported outcome (PRO) measure database of the institution was queried for all primary THAs from 2018 to 2019. The PRO measure that was utilized was the Hip disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS-JR). Cost was evaluated with use of time-driven activity-based costing (TDABC) for a 1-year episode of care (consisting of the day of surgery, inpatient stay, discharge facility, postoperative appointments, and physical therapy). The primary outcome was the 1-year value quotient, or the ratio of the 1-year change in HOOS-JR to the cost of the episode of care (V HOOS ). The value quotient was compared among all included patients and evaluated for variables that may affect the overall value of the episode of care. Results: In total, 480 patients were included in the analysis. The mean improvement in the HOOS-JR was +34.9 ± 16.1 (95% confidence interval [CI]: 33.5, 36.3). The mean cost was $13,835 ± $3,471 (95% CI: $13,524, $14,146). The largest contributor to cost was implants (39.0%), followed by post-recovery care (i.e., inpatient stay and specialized nursing facilities; 24.1%). Change in the HOOS-JR was poorly correlated with the cost of care (r = −0.06; p = 0.19). THAs performed at an ambulatory surgery center (ASC) with discharge to home demonstrated higher value (V HOOS = 0.42) than THAs performed at a hospital with discharge to a rehabilitation facility (V HOOS = 0.15; analysis of variance F-test, p < 0.01). Conclusions: Our study found that PROs did not correlate with costs in the setting of primary THA. Implants were the largest cost driver. Surgical setting (an ASC versus a hospital) and discharge destination influenced value as well. PLVA is a value measurement tool that can be utilized to optimize components of the care delivery pathway. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Many patients with malignant spinal cord compression (MSCC) who are not candidates for neurosurgery receive radiotherapy alone. This study compared 15 × 2.633 Gy over three weeks to 20 × 2.0 Gy over four weeks in patients with favorable survival prognoses. The outcomes of 34 patients treated with 15 × 2.633 Gy (equivalent dose 41.6 Gy10) in the RAMSES-01 trial were compared to 239 patients from an existing database receiving 20 × 2.0 Gy using propensity-score-adjusted Cox and logistic regression models. All patients had favorable survival prognoses. Endpoints included local progression-free survival (LPFS), improvement of motor function, post-treatment ambulatory status, and overall survival (OS). After propensity score adjustment, the 12-month rates of LPFS and OS were 98.1% (RAMSES-01 cohort) vs. 91.6% (p = 0.265) and 79.1% vs. 82.2% (p = 0.704), respectively. Regarding improvement of motor function, 15 × 2.633 Gy appeared superior (p = 0.073). No significant difference was observed regarding ambulatory status (p = 0.822). The three-week regimen for MSCC has similar outcomes and reduces treatment time when compared to a four-week regimen.

Abstract Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.

Importance Individuals with atopic dermatitis are frequently colonized and infected with Staphylococcus aureus . Empirical antibiotic therapy for individuals with atopic dermatitis is common, but data about the antimicrobial susceptibility profiles of S aureus strains isolated from these individuals are scarce for those living in particular geographic areas. Objective To determine the antimicrobial susceptibility of S aureus from individuals with atopic dermatitis and analyze differences according to the income level of the country of origin and the data collection period. Data Sources A meta-analysis of the literature was performed from the inception of the included databases (MEDLINE, Embase, Web of Science, Scopus, and Cochrane) to June 20, 2023, using predetermined Medical Subject Headings. Study Selection Studies were included if they reported antibiotic susceptibility profiles of 1 or more S aureus cutaneous isolates from individuals with atopic dermatitis. Articles written in English, Spanish, French, or German were included. Data Extraction and Synthesis Working in pairs, 6 of the authors conducted the data extraction. The guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed. Main Outcomes and Measures The outcome of interest was antimicrobial susceptibility. Results A total of 61 studies reported 4091 S aureus isolates from individuals with atopic dermatitis. For 4 of the 11 commonly used antibiotics (36.4%), antimicrobial susceptibility was 85% or less, including for methicillin (binomial proportion, 0.85 [95% CI, 0.76-0.91]), erythromycin (binomial proportion, 0.73 [95% CI, 0.61-0.83]), fusidic acid (binomial proportion, 0.80 [95% CI, 0.62-0.91]), and clindamycin (binomial proportion, 0.79 [95% CI, 0.65-0.89]). Most studies (46; 75.4%) were conducted in high-income countries. Antimicrobial susceptibility to erythromycin, methicillin, and trimethoprim and sulfamethoxazole was significantly lower in lower middle–income countries and upper middle–income countries. Regarding the temporal trends, 33 studies (54.1%) reported data collected from 1998 to 2010. Antimicrobial susceptibility patterns have not changed over time. Conclusions and Relevance In this systematic review and meta-analysis, antimicrobial susceptibility of S aureus to β-lactams, erythromycin, clindamycin, and fusidic acid may be suboptimal for empirical use in individuals with atopic dermatitis. Significant differences in antimicrobial susceptibility patterns were found in high-income countries and in lower middle–income countries and upper middle–income countries for some antibiotics.

Abstract Objectives Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome. Methods Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first AKI event. For patients with a kidney biopsy, histopathologic findings were reviewed. Results Eighty-one patients were included, all white men, with a mean age of 66.3 ± 8.6 years. Median (IQR) follow up was 3.5 (2.1–5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80–11.3%), 16.7% (7.5–25.0%) and 27.9% (14.9–38.9%), respectively. Age and baseline C-reactive protein (CRP) were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1) and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering. Conclusion AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding.

Abstract Background and Aims Severe tricuspid regurgitation is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from the surgery. Methods In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional tricuspid regurgitation (33 centres, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4–5, and high: ≥6). Results One thousand and two hundred seventeen were managed conservatively, and 551 underwent isolated tricuspid valve surgery (200 repairs and 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management [41% vs. 36%; hazard ratio (HR) .97; 95% confidence interval (CI) .88–1.08, P = .57]. Surgery improved survival compared with conservative management in the low TRI-SCORE category (72% vs. 44%; HR .27; 95% CI .20–.37, P &lt; .0001), but not in the intermediate (36% vs. 37%; HR 1.17; 95%CI .98–1.40, P = .09) or high categories (20% vs. 24%; HR 1.06; 95% CI .91–1.25, P = .45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR .11; 95% CI .06–.19, P &lt; .0001, and HR .65; 95% CI .47–.90, P = .009). Repair showed benefit in the intermediate category (59% vs. 37%; HR .49; 95% CI .35–.68, P &lt; .0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18–1.72, P = .0002). Conclusions Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials.

OBJECTIVE Common peroneal (fibular) neuropathy is the most common mononeuropathy of the lower extremity. Despite this, there are surprisingly few studies on the topic, and a knowledge gap remains in the literature. As one attempts to address this knowledge gap, a core outcome set (COS) is needed to guide the planning phases of future studies to allow synthesis and comparability of these studies. The objective of this study was to develop the COS–common peroneal neuropathy (CoPe) using a modified Delphi approach. METHODS A 5-stage approach was used to develop the COS-CoPe: 1) stage 1, consortium development; 2) stage 2, a literature review to identify potential outcome measures; 3) stage 3, a Delphi survey to develop consensus on outcomes for inclusion; 4) stage 4, a Delphi survey to develop definitions; and 5) stage 5, a consensus meeting to finalize COS and definitions. The study followed the COS–STAndards for Development (COS-STAD) recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-CoPe consisted of 31 data points/outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months. The consensus optimal time points for assessment were preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-CoPe should serve as a minimum set of data that should be collected in all future neurosurgical studies on common peroneal neuropathy. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.